Anti-CXCR4 antibodies and antibody-drug conjugates

Abstract

The present invention provides antibodies and related molecules that bind to chemokine receptor 4 (CXCR4). The invention further provides antibody-drug conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and anti-CXCR4 antibody-drug conjugates for the treatment of a disorder associated with CXCR4 function or expression (e.g., cancer), such as colon, RCC, esophageal, gastric, head and neck, lung, ovarian, pancreatic cancer or hematological cancers.

It is claimed: 
     
       1. An isolated polynucleotide comprising a nucleotide sequence encoding an antibody, or an antigen binding fragment thereof, that binds to chemokine receptor 4 (CXCR4) and comprises:
 a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising SEQ ID NO:107, 113, or 114; (ii) a VH CDR2 comprising SEQ ID NO: 162 or 128; and (iii) a VH CDR3 comprising SEQ ID NO: 112; and; 
 b) a light chain variable region (VL) region comprising (i) a VL CDR1 comprising SEQ ID NO: 144; (ii) a VL CDR2 comprising 145; and (iii) a VL CDR3 comprising SEQ ID NO: 139. 
 
     
     
       2. A vector comprising the polynucleotide of  claim 1 . 
     
     
       3. An isolated host cell that recombinantly produces the antibody or antigen binding fragment thereof of  claim 1 . 
     
     
       4. A method of producing an antibody or antigen binding fragment thereof, comprising culturing the host cell of  claim 3  under conditions that result in production of the antibody or antigen binding fragment thereof, and isolating the antibody or antigen binding fragment thereof from the host cell or culture medium.